Extent of Extraskeletal Manifestations of Fibrous Dysplasia/McCune-Albright Syndrome in Patients with Mazabraud's Syndrome.

Mazabraud's syndrome (MZB) is a rare condition in which fibrous dysplasia of bone/the McCune-Albright syndrome (FD/MAS) co-exists with intramuscular myxomas. Both FD and the myxomas harbor the GNAS-mutation. Recent studies have shown that extraskeletal, GNAS-related features are associated with a more severe phenotype of FD/MAS. However, patients with MZB are often only seen by orthopedic surgeons. We therefore evaluated MZB patients seen in tertiary referral centers from the Netherlands (LUMC), USA (National Institutes of Health) and France (INSERM UMR 1033 (Lyos), Hôpital Edouard Herriot). All FD/MAS patients known in these centers with an additional diagnosis of a myxoma were included. Demographic information and data on disease extent and extraskeletal manifestations of FD/MAS such as precocious puberty (PP) or café-au-lait patches (CAL) were retrieved from patient's medical records. Thirty MZB patients were included: 20 women (67%) and 10 men (33%). Patients received a diagnosis of MZB (median 42 years, range 16-19) significantly later than the diagnosis of FD/MAS (median 30 years, range 0-60), p < 0.01. Twenty-six patients were diagnosed with polyostotic disease (87%). In 97% the myxoma was located near the skeletal FD lesion. The combination of MZB and MAS was made in 13 patients in whom PP (n = 7), CAL (n = 7), GH-excess (n = 3) and hyperthyroidism (n = 3) were present. Other extraskeletal features were (multinodular) goiter (n = 2) and thyroid cysts (n = 1). Furthermore, in this cohort of patients with MZB several (pre-)malignant tumors were observed; ductal carcinoma in situ of the breast in 3 patients (10%), breast cancer in 1 patient (3.3%), intra pancreatic mucinous neoplasms in 3 patients (10%) and liver adenomas in 2 patients (6.6%). A total of 47% of patients with MZB had an additional extraskeletal feature such as an endocrinopathy. In MZB, 87% of patients suffer from polyostotic FD, 43% of patients have extraskeletal GNAS-features such as an hyperfunctioning endocrinopathy and 30% (pre-)malignant tumors. We therefore advocate that MZB patients should undergo a complete screening and long-term follow-up for extent of bone disease, but also extraskeletal GNAS features of FD/MAS.

Increased Prevalence of Malignancies in Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS): Data from a National Referral Center and the Dutch National Pathology Registry (PALGA).

Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated.

Individual risk evaluation for local recurrence and distant metastasis in Ewing sarcoma: A multistate model: A multistate model for Ewing sarcoma.

BACKGROUND: We investigated the effects of surgical margins, histological response, and radiotherapy on local recurrence (LR), distant metastasis (DM), and survival in Ewing sarcoma. PROCEDURE: Disease evolution was retrospectively studied in 982 patients with Ewing sarcoma undergoing surgery after chemotherapy using a multistate model with initial state surgery, intermediate states LR, pulmonary metastasis (DMpulm), other DM ± LR (DMother), and final state death. Effect of risk factors was estimated using Cox proportional hazard models. RESULTS: The median follow-up was 7.6 years (95% CI, 7.2-8.0). Risk factors for LR are pelvic location, HR 2.04 (1.10-3.80), marginal/intralesional resection, HR 2.28 (1.25-4.16), and radiotherapy, HR 0.52 (0.28-0.95); for DMpulm the risk factors are <90% necrosis, HR 2.13 (1.13-4.00), and previous pulmonary metastasis, HR 4.90 (2.28-8.52); for DMother are 90% to 99% necrosis, HR 1.56 (1.09-2.23), <90% necrosis, HR 2.66 (1.87-3.79), previous bone/other metastasis, HR 3.08 (2.03-4.70); and risk factors for death without LR/DM are pulmonary metastasis, HR 8.08 (4.01-16.29), bone/other metastasis, HR 10.23 (4.90-21.36), and <90% necrosis, HR 6.35 (3.18-12.69). Early LR (0-24 months) negatively influences survival, HR 3.79 (1.34-10.76). Once DMpulm/DMother arise only previous bone/other metastasis remain prognostic for death, HR 1.74 (1.10-2.75). CONCLUSION: Disease extent and histological response are risk factors for progression to DM or death. Tumor site and surgical margins are risk factors for LR. If disease progression occurs, previous risk factors lose their relevance. In case of isolated LR, time to recurrence is important for decision-making. Radiotherapy seems protective for LR especially in pelvic/axial. Low percentages of LR in extremity tumors and associated toxicity question the need for radiotherapy in extremity Ewing sarcoma.

18F-FDG PET-CT versus MRI for detection of skeletal metastasis in Ewing sarcoma.

OBJECTIVE: To determine the level of discrepancy between magnetic resonance imaging (MRI) and 18F-FDG PET-CT in detecting osseous metastases in patients with Ewing sarcoma. METHODS: Twenty patients with histopathologically confirmed Ewing sarcoma between 2000 and 2017 who underwent 18F-FDG PET-CT and MRI within a 4-week range were included. Each imaging modality was evaluated by a separate observer. Reference diagnosis of each lesion was based on histopathology or consensus of an expert panel using all available data, including at least 6 months' follow-up. Sensitivity, specificity, and predictive values were determined. Osseous lesions were analyzed on a patient and a lesion basis. Factors possibly related to false-negative findings were evaluated using Pearson's Chi-squared or Fisher's exact test. RESULTS: A total of 112 osseous lesions were diagnosed in 13 patients, 107 malignant and 5 benign. Seven patients showed no metastases on either 18F-FDG PET-CT or MRI. Forty-one skeletal metastases (39%) detected with MRI did not show increased 18F-FDG uptake on 18F-FDG PET-CT (false-negative). Lesion-based sensitivities and specificities were 62% (95%CI 52-71%) and 100% (48-100%) for 18F-FDG PET-CT; and 99% (97-100%) and 100% (48-100%) for MRI respectively. Bone lesions were more likely to be false-negative on 18F-FDG PET-CT if hematopoietic bone marrow extension was widespread and active (p = 0.001), during or after (neo)-adjuvant treatment (p = 0.001) or when the lesion was smaller than 10 mm (p < 0.001). CONCLUSION: Although no definite conclusions can be drawn from this small retrospective study, it shows that caution is needed when using 18F-FDG PET-CT for diagnosing skeletal metastases in Ewing sarcoma. Poor contrast between metastases and active hematopoietic bone marrow, chemotherapeutic treatment, and/or small size significantly decrease the diagnostic yield of 18F-FDG PET-CT, but not of MRI.

Illness Perceptions are Associated with Quality of Life in Patients with Fibrous Dysplasia.

Fibrous dysplasia (FD) is a rare bone disorder in which normal bone is replaced by fibrous tissue resulting in pain, deformities, pathological fractures or asymptomatic disease. Illness perceptions are patients' cognitions and emotions about their illness and its treatment, which may impact on Quality of Life (QoL). Here, we explore illness perceptions in patients with FD compared to other disorders, identify factors associated with illness perceptions and evaluate their relationship with QoL. Ninety-seven out of 138 eligible patients from the LUMC FD cohort completed the Illness Perception Questionnaire-Revised (IPQ-R) and the Short Form-36 (SF-36). Age, Gender, Skeletal Burden Score (SBS), FGF-23 levels, type of FD and SF-36 scores were analysed for an association with illness perceptions. We observed significant (p < 0.01) differences in patients' illness perceptions between FD subtypes in the domains: identity, timeline acute/chronic and consequences. Patients with craniofacial FD reported to perceive more consequences (p = 0.022). High SBS was associated with perceiving more negative consequences and attributing the cause of FD to psychological factors (p < 0.01), and high FGF-23 levels with attributing more symptoms to the disease and perceiving more consequences (p < 0.01). The IPQ-R domain identity, timeline acute/chronic, timeline cyclical, consequences, emotional representations and treatment control were significantly associated with impairments in QoL. Illness perceptions in patients with FD relate to QoL, differ from those in patients with other disorders, and are associated with disease severity. Identifying and addressing maladaptive illness perceptions may improve quality of life in patients with FD.

Passive Coping Strategies Are Associated With More Impairment In Quality Of Life In Patients With Fibrous Dysplasia.

Impairments in quality of life (QoL) have been reported in patients with fibrous dysplasia (FD). Here, we examine coping strategies in FD and assess whether these coping strategies are associated with QoL and disease severity. Ninety-two patients (66% females) filled out the Utrecht Coping List (UCL), Short Form-36, and the Brief Pain Inventory (BPI). Coping strategies of patients with FD were compared with reference data from a random sample of Dutch women and patients with chronic pain. Compared to healthy adults, patients expressed more emotions (p < 0.01). Compared to patients with chronic pain, patients with FD used more active coping strategies (p < 0.001), and sought more distraction (p = 0.01) and more social support (p < 0.001). Using more passive coping strategies was associated with more impairment in social function, physical role, mental health, vitality (all p < 0.001), and general health (p < 0.01). Using more avoidant coping strategies was associated with worse mental health and less vitality (both p < 0.01). More expression of emotions was associated with worse mental health (p < 0.01). Type and clinical severity of FD were not associated with coping behavior. Patients with FD have different coping strategies compared to random Dutch reference populations with or without pain. In FD, using more passive coping strategies was associated with more impairment in several aspects of QoL. There was no relationship between coping behavior and clinical characteristics, pointing to biomedical variables not determining the way patients cope with their illness. Recognition of less effective coping strategies can be helpful in the understanding and adaptation of these coping strategies, improving personalized clinical care, with the ultimate goal to improve QoL in patients with FD.

Chordoma: a systematic review of the epidemiology and clinical prognostic factors predicting progression-free and overall survival.

BACKGROUND AND AIMS: The aim of this systematic review is to describe the epidemiology of chordoma and to provide a clear overview of clinical prognostic factors predicting progression-free and overall survival. METHODS: Four databases of medical literature were searched. Separate searches were performed for each of the two objectives. Reference and citation tracking was performed. Papers were processed by two independent reviewers according to a protocol that included risk of bias analysis. Disagreement was resolved by discussion. Pooled analyses were planned if homogeneity of data would allow. RESULTS: Incidence-incidence rates ranged between 0.18 and 0.84 per million persons per year and varied between countries and presumably between races. On average patients were diagnosed in their late fifties and gender data indicate clear male predominance. Two of the largest studies (n = 400 and n = 544) reported different anatomical distributions: one reporting the skull base and sacrococcygeal area affected in 32% and 29% of cases, whereas the other reporting that they were affected in 26% and 45% of cases, respectively. PROGNOSTIC FACTORS: Statistically significant adverse prognostic factors predicting progression-free and overall survival include female sex, older age, bigger tumour size, increasing extent of tumour invasion, non-total resection, presence of metastasis, local recurrence, and dedifferentiated histological subtype. CONCLUSIONS: Incidence rate and anatomical distribution vary between countries and presumably between races. Most chordomas arise in the skull base and sacrococcygeal spine, and the tumour shows clear male predominance. Multiple adverse prognostic factors predicting progression-free and overall survival were identified in subgroups of patients. These slides can be retrieved under Electronic Supplementary Material.

A systematic review of prognostic factors predicting survival in patients with spinal bone metastases.

PURPOSE: For the selection of treatment in patients with spinal bone metastases (SBM), survival estimation plays a crucial role to avoid over- and under-treatment. To aid clinicians in this difficult task, several prediction models have been developed, consisting of many different risk factors. The aim of this systematic review was to identify prognostic factors that are associated with survival in patients with SBM to support development of predictive models. METHODS: A systematic review was performed with focus on prognostic factors associated with survival in patients with SBM. Two reviewers independently selected studies for inclusion and assessed the risk of bias. A level of evidence synthesis was performed for each prognostic factor. Inter-observer agreement for the risk of bias assessment was determined by the kappa-statistic. RESULTS: After screening, 142 full-text articles were obtained, of which 22 met the eligibility criteria. A total of 43 different prognostic factors were investigated in the included studies, of which 17 were relevant to pre-treatment survival estimation. The prognostic factors most frequently associated with survival were the primary tumor and the performance status. The prognostic factors most frequently not associated with survival were age, gender, number and location of the SBM and the presence of a pathologic fracture. CONCLUSIONS: Prognostication for patients with SBM should be based on an accurate primary tumor classification, combined with a performance score. The benefit of adding other prognostic factors is doubtful.

Quality of life after bone sarcoma surgery around the knee: A long-term follow-up study.

It remains unclear if quality of life (QoL) improvements could be expected in young patients after malignant bone tumour surgery after 2 years. To assess the course of QoL over time during a long-term follow-up, malignant bone tumour survivors of a previous short-term study were included. Assessments were done at least 5 years after surgery. QoL was measured with Short-form (SF)-36, TNO-AZL Questionnaire for Adult's Quality of Life (TAAQOL) and Bone tumour (Bt)-DUX. QoL throughout the follow-up was analysed by linear mixed model analysis. From the original cohort of 44 patients; 20 patients were included for this study, 10 males; mean age at surgery 15.1 years and mean follow-up 7.2 years. Twenty-one patients of the initial cohort (47%) deceased. Fifteen patients (75%) underwent limb-salvage and five (25%) ablative surgery. QoL improved significantly during follow-up at Physical Component Summary Scale scale of the SF-36 and TAAQOL and all subscales of the Bt-DUX (p < .01). No significant differences were found between current evaluations and previous evaluations at 2 years after surgery (p = .41-.98). Significant advantages after limb-salvage were seen at the PCS scale of the SF-36 (MD 13.7, p = .05) and the cosmetic scale of the Bt-DUX (MD 17.7, p = .04).

What Is the Role of Allogeneic Cortical Strut Grafts in the Treatment of Fibrous Dysplasia of the Proximal Femur?

BACKGROUND: Fibrous dysplasia of the proximal femur is a progressive, often recurrent condition of bone that can cause skeletal deformity, fractures, and pain [corrected]. Allogeneic cortical strut grafting to minimize the risk of fracture or as part of fracture treatment is a promising treatment option, but evidence is scarce on the intermediate- to long-term results of this procedure and there are no data on factors associated with graft failure. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate the revision-free survivorship; (2) radiographic findings; (3) factors associated with failure; and (4) complications associated with cortical strut allograft to prevent or treat fractures of the proximal femur in patients with fibrous dysplasia. METHODS: Between 1980 and 2013 we performed cortical strut allografting in 30 patients for impending or actual fractures of the proximal femur, of whom 28 (93%) were available for followup at a minimum of 2 years (mean, 13 years; range, 4-37 years) and of whom 22 (73%) had also been evaluated within the last 5 years. During that time, the indications for cortical strut allografting were an impending fracture of the proximal femur, persistent pain, or an actual nondisplaced femoral fracture. In patients who presented with a diaphyseal fracture, a fracture with severe dislocation of severe varus deformity, which required an osteotomy, placement of a blade plate was instead performed and these patients are not included here. During that time, for patients with diaphyseal fractures, and in patients with a displaced femoral fracture of the proximal femur, placement of a blade plate without strut grafting was instead performed; these patients are not included here. The primary outcome was the success rate of allogeneic cortical strut grafting surgery as assessed by the absence of revision surgery for a newly sustained fracture, resorption of the graft, or progressive deformity of the proximal femur. The association of possible contributing factors to graft failure such as gender, age at surgery, preoperative fracture, and anchoring distances of the graft in healthy bone was also evaluated using Cox regression analysis. RESULTS: Revision surgery was performed in 13 patients, resulting in a mean survival time of 13 years (Kaplan-Meier 95% confidence interval [CI], 10-16). Radiological resorption of the graft was observed in 15 of 28 patients (54%). However, revision surgery was not performed in all patients who developed graft resorption, because of the absence of a risk for fracture on the basis of the anatomical site of resorption. Identified risk factors for graft failure included preoperative fractures (hazard ratio [HR], 4.5; 95% CI, 1.2-17.2; p = 0.028) and insufficient proximal anchoring of the graft in healthy bone (HR, 6.02; 95% CI, 1.3-27; p = 0.02). One patient sustained a refracture after surgery resulting from an in-hospital fall. The fracture was treated without further surgery, and it healed. CONCLUSIONS: Our findings from this study suggest that cortical strut allografting may be a viable option for treatment of fibrous dysplasia of the proximal femur a without previous pathological fracture. Surgeons should pay particular attention to the proximal fixation point of the allograft to decrease the risk of failure. Patients with a fracture have an increased risk of failure and reoperation and so should be treated with an osteosynthesis. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Giant cell tumors of the sacrum--a nationwide study on midterm results in 26 patients after intralesional excision.

PURPOSE: Evaluation of recurrences, complications and function at mid-term follow-up after curettage for sacral giant cell tumor (GCT). METHODS: We retrospectively studied all 26 patients treated for sacral GCT in the Netherlands (from 1990 to 2010). Median follow-up was 98 (6-229) months. All patients underwent intralesional excision, 21 with local adjuvants, 5 radiotherapy, 3 IFN-α, 1 bisphosphonates. Functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) score. Statistics were performed with Kaplan-Meier, Cox regression, log rank and Mann-Whitney U. RESULTS: Recurrence rate was 14/26 after median 13 (3-139) months and was highest after isolated curettage (4/5). Soft tissue masses >10 cm increased recurrence risk (HR = 3.3, 95 % CI = 0.81-13, p = 0.09). Complications were reported in 12/26 patients. MSTS was superior in patients without complications (27 vs. 21; p = 0.024). CONCLUSION: Recurrence rate for sacral GCT was highest after isolated curettage, indicating that (local) adjuvant treatment is desired to obtain immediate local control. Complications were common and impaired function.

Risk factors for survival of 106 surgically treated patients with symptomatic spinal epidural metastases.

PURPOSE: Evaluation of risk factors for survival in patients surgically treated for symptomatic spinal epidural metastases (SEM). METHODS: One hundred and six patients who were surgically treated for symptomatic SEM in a 10-year period in two cooperatively working hospitals were retrospectively studied for nine risk factors: age, gender, site of the primary tumor, location of the symptomatic spinal metastasis, functional and neurologic status, the presence of visceral metastases and the presence of other spinal and extraspinal bone metastases. Analysis was performed using the Kaplan-Meier method, univariate log-rank tests and Cox-regression models. RESULTS: Overall median survival was 10.7 months (0.2-107.5 months). Overall 30-day complication rate was 33 %. Multivariate Cox-regression analysis showed that fast growing primary tumors (HR 3.1, 95 % CI 1.6-6.2, p = 0.001), the presence of visceral metastases (HR 1.7, 95 % CI 1.0-2.9, p = 0.033) and a low performance status (HR 2.7, 95 % CI 1.1-6.6, p = 0.025) negatively influenced the survival. CONCLUSION: Primary tumor type, presence of visceral metastases and performance status are significant predictors for survival after surgery for symptomatic SEM and should be evaluated before deciding on the extent of treatment. More accurate prediction models are needed to select the best treatment option for the individual patient.

Poor long-term clinical results of saddle prosthesis after resection of periacetabular tumors.

BACKGROUND: The saddle prosthesis originally was developed to reconstruct large acetabular defects in revision hip arthroplasty and was used primarily for hip reconstruction after periacetabular tumor resections. The long-term survival of these reconstructions is unclear. QUESTIONS/PURPOSE: We therefore examined the long-term function, complications, and survival in patients treated with saddle prostheses after periacetabular tumor resection. PATIENTS AND METHODS: Between 1987 and 2003 we treated 17 patients with a saddle prosthesis after periacetabular tumor resection (12 chondrosarcomas, three osteosarcomas, one malignant fibrous histiocytoma, one metastasis). During followup, 11 patients died, resulting in a median overall survival of 49 months (95% CI, 30-68 months). The remaining six patients were alive without disease (mean followup, 12.1 years; range, 8.3-16.8 years). In one patient the saddle prosthesis was removed after 3 months owing to dislocation and infection. We obtained SF-36 questionnaires, Toronto Extremity Salvage Scores (TESS), and Musculoskeletal Tumor Society (MSTS) scores. RESULTS: Thirteen of 17 patients used walking assists for mobilization at last followup: eight patients required two crutches, five needed one crutch, and one did not use any walking aids. The other three patients were not able to mobilize independently and only made bed to chair transfers. The mean hip flexion in the six surviving patients was 60° (range, 40°-100°) at last followup. Local complications were seen in 14 of the 17 patients: nine wound infections, seven dislocations, and two leg-length discrepancies requiring additional surgery. In the five surviving patients with their index prosthesis still in situ, the mean MSTS score at long-term followup was 47% (range, 20%-77%), the mean TESS score was 53% (range, 41%-67%), and the mean composite SF-36 physical and mental component summaries were 43.9 and 50.6, respectively. CONCLUSION: Reconstruction with saddle prostheses after periacetabular tumor surgery has a high risk of complications and poor long-term function with limited hip flexion; therefore, we no longer use the saddle prosthesis for reconstruction after periacetabular tumor resections.

Presacral myelolipoma, case report and literature review.

INTRODUCTION: Myelolipomas are very rare benign tumours consisting of hematopoietic cells and mature adipose tissues. They are most commonly found in the adrenal glands. However, there have been several reported cases of extra-adrenal myelolipomas, most commonly in the presacral region. Nearly all presacral lesions are small and asymptomatic; thus, most are discovered incidentally on imaging studies. PRESENTATION OF CASE: We report two cases of presacral myelolipomas. The first is a 48-year-old female presenting with atypical back pain, found to have a mass in her presacral region with a size of 3,3 cm. The second case is a 59-year-old female, who presented for evaluation of a hip fracture, found to have a 4,7 cm presacral lesion. Both presacral myelolipomas were discovered incidentally and were confirmed by percutaneous guided fine-needle aspiration biopsy. Both were treated conservatively. DISCUSSION: Accepted indications for the surgical excision of myelolipomas are symptomatic tumour, size >4 cm, metabolically active tumour, and a suspicion of malignancy on an imaging study. However, previous reports have documented that nearly half of the conservatively managed myelolipomas with a mean initial size of 5,1 cm, has increased in size or became symptomatic over a 3-years period. CONCLUSION: We conclude that symptomatic presacral myelolipomas or lesions larger than 4 cm should be en-bloc resected, and we present an intuitive decision-making algorithm.

Long-Term Clinical Outcomes of Intercalary Allograft Reconstruction for Lower-Extremity Bone Tumors.

BACKGROUND: Improved survival rates for patients with primary bone tumors of the extremities have increased the demand for reliable and durable reconstruction techniques. Some authors have stated that, after successful ingrowth, allografts are a durable long-term solution. This hypothesis is largely based on small studies with short-to-midterm follow-up. In order to determine the durability of intercalary allograft reconstructions in the lower extremities, we evaluated the long-term clinical outcomes at a minimum of 10 years. METHODS: All patients who received an intercalary allograft reconstruction in a lower extremity between 1980 and 2006 were included in this retrospective multicenter cohort study. One hundred and thirty-one patients with a median age of 19 years were included. Eighty-nine (68%) had a femoral reconstruction, and 42 (32%) had a tibial reconstruction. The most prevalent diagnoses were osteosarcoma (55%), Ewing sarcoma (17%), and chondrosarcoma (12%). The median follow-up was 14 years. A competing risk model was employed to estimate the cumulative incidences of mechanical failure and infection. Patient mortality or progression of the disease was used as a competing event. RESULTS: Nonunion occurred in 21 reconstructions (16%), after a median of 16 months, and was associated with intramedullary nail-only fixation (p < 0.01) and fixation with nonbridging plate(s) (p = 0.03). Allograft fracture occurred in 25 reconstructions (19%) after a median of 42 months (range, 4 days to 21.9 years). Thirteen (52%) of the allograft fractures occurred within 5 years; 8 (32%), between 5 and 10 years; and 4 (16%), at >10 years. With failure for mechanical reasons as the end point, the cumulative incidences of reconstruction failure at 5, 10, and 15 years were 9%, 14%, and 21%, respectively. CONCLUSIONS: Intercalary allograft reconstruction is an acceptable reconstructive option, mainly because of the absence of superior alternatives with a known track record. However, a considerable and continuing risk of mechanical complications should be taken into account. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Axial cortical involvement of metastatic lesions to identify impending femoral fractures; a clinical validation study.

BACKGROUND AND PURPOSE: Patients with advanced cancer may develop painful bone metastases, potentially resulting in pathological fractures. Adequate fracture risk assessment is of key importance to prevent fracturing and maintain mobility. This study aims to validate the clinical reliability of axial cortical involvement with a 30 mm threshold on conventional radiographs to assess fracture risk in femoral bone metastases. MATERIALS AND METHODS: All patients with bone metastases who received radiotherapy for pain included in two multicentre prospective studies were selected. Conventional radiographs obtained at a maximum of two months prior to radiotherapy were collected. Three experts independently measured lesions and scored radiographic characteristics. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated. RESULTS: Hundred patients were included with a median follow-up of 23.0 months (95%CI: 10.6-35.5). Two fractures occurred in lesions with axial cortical involvement <30 mm, and 12 in lesions ≥30 mm. Sensitivity, specificity, PPV and NPV of axial cortical involvement for predicting femoral fractures were 86%, 50%, 20% and 96%, respectively. Patients with lesions ≥30 mm had a 5.3 times higher fracture risk than patients with smaller lesions. CONCLUSION: Our validation study confirmed the use of 30 mm axial cortical involvement to assess fracture risk in femoral bone metastases. Until a more accurate and practically feasible method has been developed, this clinical parameter remains an easy method to assess femoral fracture risk to aid patients and clinicians to choose the optimal individual treatment modality.

Surgical Outcome and Oncological Survival of Osteofibrous Dysplasia-Like and Classic Adamantinomas: An International Multicenter Study of 318 Cases.

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Easy-to-use clinical tool for survival estimation in Ewing sarcoma at diagnosis and after surgery.

Accurate survival estimations in Ewing sarcoma are necessary to develop risk- and response adaptive treatment strategies allowing for early decision-making. We aim to develop an easy-to-use survival estimation tool from diagnosis and surgery. A retrospective study of 1314 Ewing sarcoma patients was performed. Associations between prognostic variables at diagnosis/surgery and overall survival (OS), were investigated using Kaplan-Meier and multivariate Cox models. Predictive accuracy was evaluated by cross-validation and Harrell C-statistics. Median follow-up was 7.9 years (95%CI 7.6-8.3). Independent prognostic factors at diagnosis were age, volume, primary tumor localization and disease extent. 5 risk categories (A-E) were identified with 5-year OS of 88% (86-94), 69% (64-74), 57% (50-64), 51% (42-60) and 28% (22-34) respectively. Harrell C-statistic was 0.70. Independent prognostic factors from surgery were age, volume, disease extent and histological response. In categories A-B, 5y OS increased to 92% (87-97) and 79% (71-87) respectively for 100% necrosis and decreased to 76% (67-85) and 62% (55-69) respectively for <100% necrosis. In categories C-E, 5y OS increased to 65% (55-75), 65% (52-78) and 52% (38-66) respectively for ≥90% necrosis and decreased to 38% (22-54), 11% (0-26) and 7% (0-19) respectively for <90% necrosis. We present an easy-to-use survival estimation tool from diagnosis in Ewing sarcoma based on age, volume, primary tumor localization and disease extent. Histological response is a strong additional prognostic factor for OS.

Multiflora and Gram-Negative Microorganisms Predominate in Infections Affecting Pelvic Endoprostheses Following Tumor Resection.

BACKGROUND: Periprosthetic infections after pelvic reconstruction are common, with reported rates ranging from 11% to 53%. Management of these infections is troublesome, as they commonly necessitate multiple surgical interventions and implant removal. The epidemiology and outcomes of these infections are largely unknown. The aim of this study was to analyze the causative microorganisms and the clinical outcome of treatment in a series of patients with pelvic endoprostheses affected by infection following tumor resection. METHODS: In this retrospective, multicenter cohort study, we identified all patients who developed an infection after endoprosthetic reconstruction in periacetabular tumor resection, between 2003 and 2017. The microorganisms that were isolated during the first debridement were recorded, as were the number of reoperations for ongoing infection, the antimicrobial treatment strategy, and the outcome of treatment. RESULTS: In a series of 70 patients who underwent pelvic endoprosthetic reconstruction, 18 (26%) developed an infection. The type of pelvic resection according to the Enneking-Dunham classification was type P2-3 in 14 (78%) of these patients and type P2 in 4 (22%). Median follow-up was 66 months. Fourteen (78%) of the 18 patients with infection had a polymicrobial infection. Enterobacteriaceae were identified on culture for 12 (67%). Of a total 42 times that a microorganism was isolated, the identified pathogen was gram-negative in 26 instances (62%). Microorganisms associated with intestinal flora were identified 32 times (76%). At the time of latest follow-up, 9 (50%) of the patients had the original implant in situ. Of these, 2 had a fistula and another 2 were receiving suppressive antibiotic therapy. In the remaining 9 (50%) of the patients, the original implant had been removed. At the time of final follow-up, 3 of these had a second implant in situ. The remaining 6 patients had undergone no secondary reconstruction. CONCLUSIONS: Infections that affect pelvic endoprostheses are predominantly polymicrobial and caused by gram-negative microorganisms, and may be associated with intestinal flora. This differs fundamentally from mono-bacterial gram-positive causes of conventional periprosthetic joint infections and may indicate a different pathogenesis. Our results suggest that prophylaxis and empiric treatment may need to be re-evaluated. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.